Effect of Intermittent Subglottic Irrigation with 5% NaCl on the Prevention of Ventilator Associated Pneumonia in Critically Ill Patients.

Background: Ventilator-Associated Pneumonia (VAP) is one of the common causes of mortality and morbidity. Subglottic secretion suction decreases the incidence of VAP. In this study, the effect of 5% sodium chloride (NaCl) in subglottic area in addition to secretion suction in VAP prevention was investigated in patients who were admitted to the intensive care unit. Materials and Methods: All patients were intubated by an intubation tube with subglottic suction. In the intervention group, subglottic area was washed with 10 ml of 5% sodium chloride solution, and in the control group the subglottic area was washed with 10 ml distilled water. Patients were monitored for a maximum of two weeks, and the incidence of VAP was monitored by a Clinical Pulmonary Infection Score (CPIS). Results: There was no significant difference between the two groups in terms of age and sex. Four (27%) patients in the intervention group, and 7 (37%) in control group were diagnosed with VAP, which was not statistically significant between the two groups (P=0.225). The duration of hospitalization, duration of intubation and mortality did not show any significant difference between the two groups. Conclusion: It was expected that in this study the rate of VAP became significantly lower with the intervention of using antimicrobial solution in addition to suction. Although the rate decreased clinically, it was not statistically significant, which may be due to the low number of patients.


INTRODUCTION
Ventilator-Associated Pneumonia (VAP) is a serious and common disorder in the Intensive Care Unit (ICU). The incidence of VAP is 9-27% in critically ill patients who are under mechanical ventilation. VAP remains a major contributor to morbidity and mortality in intubated patients (1). It is associated with dangerous complications in this group of patients. These complications include prolonged ventilation support, ICU and hospital length of stay, and increased healthcare cost (2,3). Pathogenic microorganisms that colonize the oropharyngeal region are the most important cause of VAP (4). One of the important ways which predisposes patients to VAP is micro aspiration of subglottic secretions that are above the cuff of endotracheal tube. Significant changes in liquid aspiration are due to materials and design of the endotracheal tube cuff (5). After intubation, pathogenic bacteria colonize the oropharynx surfaces (6,7) and secretions rapidly accumulate above the cuff (8). By lining the cuff these secretions enter the lungs and create infection. For this reason preventive strategies for VAP are based on the colonization and aspiration modification. One of these strategies includes subglottic secretion draining. Based on these reasons a kind of endotracheal tube has been made through which secretions from the subglottic region can be suctioned. Although studies have shown that subglottic secretion suctioning decreases the incidence of VAP, it is still the most common cause of death in ICU (9). Therefore, use of an antimicrobial agent in the subglottic region may have a better effect on VAP reduction than suctioning the secretion alone.
Sodium chloride (NaCl) by increasing osmotic pressure and decreasing water activity around the microbes stops microbial growth. Although the salt environment is suitable for some bacteria, such as Staphylococcus saprophyticus, these micro-organisms cannot live in high salt concentrations. Other bacteria such as Escherichia coli have the best growth in salt-free environments and salt can severely limit its growth (10).
Many studies have shown the effect of hypertonic sodium chloride nebulizer on the improvement of cystic fibrosis patients (11). Previous studies have shown that hypertonic sodium chloride reduces the activity of Pseudomonas aeruginosa and improves patients who suffer from cystic fibrosis. It can also be effective in improving other pulmonary patients (12). It has been shown that hypertonic sodium chloride has a static and a bactericidal effect. Also, when is used topically on wounds can prevent the spread of infection (13 (14).
According to the bactericidal effect of hypertonic sodium, a comparative study was designed to indicate the effect of 5% sodium chloride injection in the subglottic region in prevention of VAP. It should be noted that as this was the first study in this regard; therefore, it was designed as a pilot study.

Study design
This study is a randomized, double-blind, placebocontrolled trial. After approval by the Ethics Committee

Randomization and blinding
Patients who met the inclusion criteria were randomly allocated (1:1) to sodium chloride or placebo group according to a randomization code listed by a computer program. In this study, patients were not aware of the treatment group due to the decreased level of consciousness. The researcher, who studied the variables, did not know the group of study, and washing of subglottic was done by a nurse.

Clinical Assessments
Patient's demographic data included age and sex, and APACHE score II was recorded at the time of admission.
All patients were intubated by suction tube (Tra-suction).
Every 8 hours, the tube cuff was adjusted between 25 and 30 cm Hg. Subglottic secretion of patients was aspirated by a lumen which was used for this purpose in the Tra-suction tube. Afterward, in the sodium chloride group, 10 ml of 5% saline solution and in the placebo group 10 ml distilled water was entered into the subglottic region through the suction lumen. The solutions were suctioned after 5 minutes. Then the tube cuff was adjusted to 20 to 25 cm Hg again. Patients were monitored for up to two weeks during mechanical ventilation. The incidence of VAP was measured by the Clinical Pulmonary Infection Score (CPIS), which was measured every three days.

Outcome
Primary outcome was the incidence of VAP during mechanical ventilation up to two weeks. Secondary outcomes were duration of mechanical ventilation, length of ICU stay and mortality during hospitalization in ICU.

Statistical analysis
In describing the quantitative variables due to the small number of samples which were not normally distributed, median (med) and Interquantile Range (IQR) were reported; moreover, qualitative variables were described by percentages. The quantitative data were compared through Mann-Whitney U test, while comparing qualitative data, the Exact test was used. Statistical significance level was set at 0.05.

Patient characteristics
Recent investigation was a pilot study. Thirty patients were enrolled in this randomized, double-blind, placebocontrolled trial. Fifteen patients were enrolled in each group. Patient characteristics were comparable in age, sex, APACHE II Score, underlying disease and cause of hospitalization upon admission (Table 1).  However, a number of studies have shown that it can increase bacterial dislodgement and can lead to its migrating into the lower airways. We increased the cuff pressure during saline instillation to prevent bacterial dislodgement, and a hyper-tonic saline was used above the cuff. However, there is a possibility that micro-aspiration could cause these inappropriate results in the recent study.
Meanwhile, as regards to low power of the study, the limited number of patients can lead to these results.
Limitations of our study were: the study was carried out in a single institute, and had a small sample size. These limitations have affected the strength of our study, but the method of analysis and its interpretation are appropriate.

CONCLUSION
It can be concluded that subglottic irrigation with 5%NaCl in addition to suction, can clinically reduce the incidence of VAP, although this reduction is not significant.